The present invention relates generally to the treatment and prophylaxis of penile dysfunction. More particularly, the present invention contemplates the treatment and prophylaxis of persistent penile erection resulting from, for example, physiological dysfunction, trauma, surgical intervention, or chemical induction. The method of the present invention is practised by the administration of an agent capable of inducing, promoting or otherwise facilitating contraction of the cavernosum. Accordingly, another aspect of the present invention provides a composition comprising a cavernosum contraction-inducing, -promoting, or -facilitating agent. In one embodiment, the agents of the present invention are prostaglandins or functional derivatives, homologues, analogues, agonists, mimetics, or metabolites thereof. This invention also provides a means for diagnosing the physiological basis behind penile dysfunction.
Priapism is defined as a prolonged, usually painful, penile erection generally not directly initiated by sexual stimulus. It results from a disturbance or other dysfunction in the normal regulatory mechanisms which initiate and maintain penile flaccidity. The treatment of this condition ranges from predominately surgical management to less invasive pharmacological therapies. Despite recent advances in the understanding of erectile mechanisms, the pathophysiology of priapism remains obscure in up to 50% of cases. See, e.g., Steers and Selby, J. Urol. 146(5): 1361-1363 (1991). Thus, in the absence of an identifiable aetiology, treatment has been essentially symptomatic. In at least 5% of patients treated for impotence, injection of vascoactive substances such as papaverine, prostagiandin E, and phenoxybenzamine (or phentolamine), an alpha-adrenergic blocking drug, into the corpora cavernosa muscle, is the most likely cause of priapism. Furthermore, the availability of sildenafil citrate (sold under the trademark xe2x80x9cViagraxe2x80x9d) as an anti-impotence drug, has resulted in its misuse as an aphrodisiac to improve male sexual performance. Reports indicate that sildenafil also has caused priapism. If left unattended, the abuse and misuse of erection-producing vasoactive agents is likely to lead to priapism and irreversible muscle damage. Other situations in which priapism is seen include disease states such as sickle cell anaemia and use of unrelated drugs such as antidepressants (e.g., trazodone).
Current antidotes for priapism are alpha-adrenoceptor agonists such as metaraminol, adrenaline, phenylephrine, noradrenaline, and ethylephrine. These alpha-mimetics are known to produce systemic side effects including a rise in systemic blood pressure. Hence, such agents are contraindicated for cardiovascular patients. Accordingly, there is a need to identify reliable, safe, and efficacious pharmacological agents for the treatment and prophylaxis of penile dysfunction characterized by prolonged penile erection.
The present invention is predicated in part on the identification of a group of compounds which induce, promote, or otherwise facilitate contraction of the cavernosum associated with penile tissue. An important feature of this invention is that the agents employed in accordance with the present invention do not cause a rise in systemic blood pressure. Particularly preferred agents include the prostaglandins such as, but not limited to, prostaglandin A2, prostaglandin A1, prostaglandin B1, and prostaglandin B2, as well as functional derivatives, homologues, analogues, agonists, mimetics, and metabolites thereof.
Accordingly, one aspect of the present invention contemplates a method for the treatment or prophylaxis of priapism in a male subject, said method comprising administering to said subject an effective amount of an agent which induces, promotes or otherwise facilitates contraction of corpora cavernosa muscle in the cavernosum, without a concomitant rise in systemic blood pressure, the administration of which agent leads to partial or complete penile flaccidity.
Another aspect of the present invention is directed to a method for the treatment or prophylaxis of priapism in a male subject said method comprising administering to said subject an effective amount of a prostaglandin or a functional derivative, homologue, analogue, agonist, mimetic, or metabolite thereof which induces, promotes, or otherwise facilitates contraction of corpora cavernosa muscle in the cavernosum, without a concomitant rise in systemic blood pressure, for a time and under conditions sufficient to lead to partial or complete penile flaccidity or to prevent or reduce the likelihood of an erection.
Yet another aspect of the present invention provides a composition for pharmaceutical use comprising an agent which induces, promotes, or otherwise facilitates contraction of corpora cavernosa muscle in the cavernosum in penile tissue, said composition further comprising one or more pharmaceutically acceptable carriers and/or diluents.
The preferred agents of the present invention are prostaglandins such as, but not limited to, prostaglandin A2, A1, B1, and B2.
The most preferred agent is prostaglandin A2 or functional derivatives, homologues, analogues, agonists, mimetics, or metabolites thereof. The terms xe2x80x9cprostaglandin A2xe2x80x9d, xe2x80x9cAdainusxe2x80x9d, xe2x80x9cAS-8xe2x80x9d, and xe2x80x9cpriapresxe2x80x9d may be used interchangeably to refer to xe2x80x9cprostaglandin A2xe2x80x9d.